CD133 antisense suppresses cancer cell growth and increases sensitivity to cisplatin in vitro

Abstract

The increased incidence of cancer in recent years is associated with a high rate of mortality. Numerous types of cancer have a low percentage of CD133+ cells, which have similar features to stem cells. The CD133 molecule is involved in apoptosis and cell proliferation. The aim of this study was to determine the biological effect of CD133 suppression and its role in the chemosensitization of cancer cell lines. RT-PCR and immunocytochemical analyses indicated that CD133 was expressed in the cancer cell lines B16F10, MCF7 and INER51. Downregulation of CD133 by transfection with an antisense sequence (As-CD133) resulted in a decrease in cancer cell viability of up to 52, 47 and 22% in B16F10, MCF-7 and INER51 cancer cell lines, respectively. This decreased viability appeared to be due to the induction of apoptosis. In addition, treatment with As-CD133 in combination with cisplatin had a synergic effect in all of the cancer cell lines analyzed, and in particular, significantly decreased the viability of B16F10 cancer cells compared with each treatment separately (3.1% viability for the combined treatment compared with 48% for 0.4 μg As-CD133 and 25% for 5 ng/μl cisplatin; P<0.05). The results indicate that the downregulation of CD133 by antisense is a potential therapeutic target for cancer and has a synergistic effect when administered with minimal doses of the chemotherapeutic drug cisplatin, suggesting that this combination strategy may be applied in cancer treatment.

Development of resistance to photodynamic therapy (PDT) in human breast cancer cells is photosensitizer-dependent: Possible mechanisms and approaches for overcoming PDT-resistance

“…CD133 is an important CSC marker, and is found glycosylated in the colorectal adenocarcinoma WiDr, breast cancer MDA-MB-231 and the melanoma cell line FEMX-1, hence being a target for the immunotoxin AC133-saporin (Paper V). The CD133 negative MCF-7 cell line was used as a negative control, although other work describes this cell line differently dependent on which CD133 antibody is used for detection (Blancas-Mosqueda, 2012). This may be related to several epitopes of CD133 recognized both on the extracellular and intracellular part of CD133 (Bidlingmaier et al, 2008).…”

Green Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma

“…[2][3][4][5] Nowadays, surgical resection is considered the first line of melanoma therapy, in addition to traditional chemotherapy, radiotherapy, immunotherapy, and biological therapy. 6 The failure of most therapeutic agents is due to the immunosuppressive [7][8][9] and stem-like 10,11 nature of B16F10 melanoma cells, in addition to the complex structure of tumor tissue. The complexity of tumor tissue is due to the tumor microenvironment (TME) which includes a variety of cellular components that contribute to tumor invasion, metastasis, and drug resistance.…”

“…CSCs exhibit high potential for tumor growth and metastasis, inhibition of apoptosis, recurrence, and resistance to different therapeutic approaches. 10 , 11 The key cellular players in the TME are tumor-associated fibroblasts (TAFs) and tumor-associated macrophages (TAMs). 13 TAFs perform multiple activities in tumor formation.…”